Alterations in chromosome structure and variations in the inherent radiation sensitivity of human cells

Variations in the inherent radiosensitivity of both tumor cells and the normal tissues that surround them play an important role in tumor response to radiation therapy. In vitro studies suggest that variations in radiation sensitivity both between different tissues and within a specific histology are a reflection of differences in the rate and fidelity of rejoining of chromosome breaks. Cells of radiosensitive cell lines rejoin breaks more slowly and with less fidelity than those of more resistant cell lines. Differences in radiation sensitivity are also associated with variations in chromosome structure as detected by nucleoid-based assays. A model is presented to suggest that the radiation sensitivity of a cell line is a reflection of its transcriptional architecture, the number and genomic location of its actively transcribing regions. Also, it is proposed that chromosome breaks induced at or near transcriptionally active regions of the genome are rejoined preferentially and with greater fidelity than breaks induced at other regions of the genome.